In:
Hormone Research in Paediatrics, S. Karger AG, Vol. 94, No. 11-12 ( 2021), p. 448-455
Abstract:
Coats plus syndrome is an autosomal recessive multisystemic and pleiotropic disorder affecting the eyes, brain, bone, and gastrointestinal tract, usually caused by compound heterozygous variants of the conserved telomere maintenance component 1 gene ( 〈 i 〉 CTC1 〈 /i 〉 ), involved in telomere homeostasis and replication. So far, most reported patients are compound heterozygous for a truncating mutation and a missense variant. The phenotype is believed to result from telomere dysfunction, with accumulation of DNA damage, cellular senescence, and stem cell depletion. Here, we report a 23-year-old female with prenatal and postnatal growth retardation, microcephaly, osteopenia, recurrent fractures, intracranial calcification, leukodystrophy, parenchymal brain cysts, bicuspid aortic valve, and primary ovarian failure. She carries a previously reported maternally inherited pathogenic variant in exon 5 (c.724_727del, p.(Lys242Leufs*41)) and a novel, paternally inherited splice site variant (c.1617+5G & #x3e;T; p.(Lys480Asnfs*17)) in intron 9. 〈 i 〉 CTC1 〈 /i 〉 transcript analysis showed that the latter resulted in skipping of exon 9. A trace of transcripts was normally spliced resulting in the presence of a low level of wild-type 〈 i 〉 CTC1 〈 /i 〉 transcripts. We speculate that ovarian failure is caused by telomere shortening or chromosome cohesion failure in oocytes and granulosa cells, with early decrease in follicular reserve. This is the first patient carrying 2 truncating 〈 i 〉 CTC1 〈 /i 〉 variants and the first presenting primary ovarian failure.
Type of Medium:
Online Resource
ISSN:
1663-2818
,
1663-2826
Language:
English
Publisher:
S. Karger AG
Publication Date:
2021
detail.hit.zdb_id:
2540224-9
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